Neuropathologic evaluation remains the "gold standard" for identifying the cause(s) of dementia. The major responsibilities of this Core are to perform the neuropathologic studies necessary to document the diagnosis of Alzheimer disease (AD) and/or other pathologic entities in all human brain specimens used in research studies proposed by investigators within and outside of the ADC, and to provide clinico-pathologic correlation for ADC Clinical Core patients. Therefore, in Specific Aim 1, we will maintain a human brain tissue bank whose mail functions will be: 1) to collect, prepare, evaluate (including ApoE genotyping), catalog, store, and distribute well-characterized postmortem brain tissue and other samples (including postmortem DNA) from deceased demented and control subjects for use in research; 2) to report qualitative and quantitative diagnostic information to physicians, families, and researchers; 3) to work with the Clinical Core to provide clinico-pathologic correlation; and 4) to regularly update the central ADC and National Alzheimer Coordinating Center (NACC) databases with diagnostic and other related information on autopsied and biopsied subjects. In order to enhance the neuropathologic characterization of brain tissue accessioned through this Core, in Specific Aim 2, we will also focus on providing extensive quantitative neuropathologic evaluations for correlation with clinical and research data. The specific analyses to be performed will include: 1) ongoing quantification of synapse density (by measuring concentration of synaptophysin) in postmortem neocortex using an enzyme-linked immunosorbant assay (ELISA) the we developed; 2) quantification of neocortical neuritic dystrophy in sections immunostained for tau and alpha-synuclein using optimized, highly sensitive and specific immunostaining techniques and computer assisted light microscopic image analysis; and 3) quantification of brain microvascular alterations, including blood vessel amyloid deposition and arteriosclerosis/lipohyalnosis and cerebral white matter density, using immunostaining and computer assisted light microscopic image analysis. The thorough neuropathologic characterization of brain tissue as proposed in this Core, utilizing a novel combination of state-of-the-art staining techniques and quantitative analyses, will provide the highest level of diagnostic certainty attainable, and ensure that appropriate tissues are used for research projects.